Apoptosis refers to programmed cell death of body cells during development or under some factors, caused by regulation of intracellular genes and products thereof. Apoptosis universally exists in biosphere, occurs under either physiological state or pathological state, and plays an important role in embryo development, morphogenesis, stabilization of normal cells in tissues, defense and immune reaction of body, cell damage caused by diseases or intoxication, aging, occurrence and development of tumors. Thus it has been a hotspot for biomedical research.
Researches indicate that occurrence of many serious diseases relate to excessive apoptosis, for example, decreased of CD4+ T cells number in development of AIDS; cell death mediated by cytotoxic T cells in graft rejection; apoptosis of myocardial cells and nerve cells in ischemia reperfusion injury; nerve system degradation diseases (e.g., Alzheimer's disease, Parkinson's disease, etc.); apoptosis of many tissue cells caused by exposing to ionizing radiation.
Some evidences show that cardiomyocyte apoptosis closely relates to occurrence, development and prognosis of many heart diseases. Researches of cardiomyocyte apoptosis show that myocardial death of infarct is not equivalent to myocardial necrosis, apoptosis is one of mechanisms of myocardial infarction, and is also main form of myocardial death in early stage of infarction and myocardial death caused by ischemia/reperfusion, and apoptosis of large amount of myocardial cells at this moment aggravate damage of cardiac muscle. In 1989, Nepomniashchikh, et al, found that in observation of ultra-structure of starved myocardial atrophy, structure protein synthesis of myocardial cells reduced, cell number decreased, but corresponding proportional decrease of cell nucleus was not accompanied, and thus it is primarily suggested that starved myocardial atrophy was caused by apoptosis. In 1994, Gottlieb and Kawano, et al, obtained direct evidence of cardiomyocyte apoptosis using electron microscope in combination with DNA gel electrophoresis, the former disclosed that reperfusion injury induced rabbit cardiomyocyte apoptosis, while the latter confirmed that myocarditis patients were accompanied with cardiomyocyte apoptosis. Tanaka, et al, also confirmed the existence of apoptosis in cultured myocardial cells of suckling mice. With the advance of methodology and intensive study of apoptosis, the pathological effects of cardiomyocyte apoptosis were found in many heart diseases. Studies showed that heart injury in spontaneous hypertension rats (SHR) was related to apoptosis; The conversion from hypertrophic heart in advanced stage to heart failure was caused by cardiomyocyte apoptosis; in acute myocardial infarction, besides necrosis, early infarction and reperfusion injury also induced apoptosis; cardiomyocyte apoptosis was also observed in transplanted heart and right ventricular dysplasia cardiomyopathy, and anoxia also induced cardiomyocyte apoptosis.
To some extents, apoptosis was reversible, cardiomyocyte apoptosis in myocardial infarction and ischemia/reperfusion has its features and rules, and these features could be used to prevent and reduce apoptosis to provide suggestions for clinical prevention of ischemia/reperfusion; during reperfusion procedure, apoptosis occurred in contraction band zone (around infarct focus) is induced by some causes, and thus inhibition factors of apoptosis, like medicament, could be used to prevent apoptosis and treat relative diseases caused by apoptosis.
However, medicament available in clinical for anti-apoptosis and cell protection is very few in sorts and quantity, and not effective in selectivity and targeting, so it is of great importance to develop new, safe and effective anti-apoptotic and cell-protective drugs, especially those with completely new mechanism of action.